Kim-1 is a type 1 transmembrane protein with an extracellular Ig domain that undergoes strong induction in the S3 segment of renal epithelial cells after renal injury. Although the function of Kim-1 in the kidney is unknown, Kim-1 is an important asthma susceptibility gene. It is proposed to be the cellular receptor for the hepatitis A virus and Kim-1 expression is upregulated in almost all renal cell carcinomas. We hypothesize that Kim-1 regulates renal epithelial cell adhesion and migration. After renal epithelial injury, induction of Kim-1 may serve to tether injured but viable cells to the basement membrane, preventing sloughing and intratubular cast formation. In the proposed studies we will characterize the intracellular localization of Kim-1 and investigate colocalization with focal adhesions. We will determine whether ectodomain shedding is necessary for Kim-1 dependent adhesion and migration. The downstream signaling pathways activated by Kim-1 will be investigated using the yeast two-hybrid approach and ligand-affinity chromatography. The proposed studies will have great relevance in understanding the molecular mechanisms of renal regeneration and renal cell cancer invasion and metastasis.